This project is designed to study genetic and immunologic factors involved in BCG-induced chronic granulomatous pulmonary inflammation and splenomegaly. The capacity to develop pulmonary inflammation and splenomegaly is restricted to certain inbred strains of mice, is dominant, multigenic, not linked to the H-2 complex and is linked to the Igh complex. This project is alsodesigned to evaluate the modulation of granulomatous inflammation by suppressor cells or factors. The development of BCG-induced pulmonary inflammation appears to be controlled by cyclophosphamide-sensitive T suppressor cells. Some mice which develop intense pulmonary inflammation develop adherent suppressor spleen cells which may suppress the inflammatory response. The development of adherent suppressor cells is also genetically controlled: it is unigenic, recessive, and also influenced by genes linked to the Igh complex. These studies are related to several human diseases in which chronic granulomatous inflammation is a prominent feature. Future studies in this animal model should provide a better understanding of chronic granulomatous inflammation in man.